The intravenous injection of F1 hybrid mice with parental spleen cells resulted in a loss in the ability of the F1 mice to generate T-cell mediated cytotoxic responses in vitro to TNP-self and alloantigens. The loss of response potential dependend on the H-2 type of the parental cells, since H-2k,a spleen cells induced unresponsiveness, whereas H-2b spleen cells did not. The phenomenon is dependent or recognition of F1 I-A alloantigens by grafted parental cells (GVH). Suppressor T cell were found to be responsible for loss of immune potential. The immune responses of F1 mice immunized with other antigens at the same time or prior to inoculation with parental cells were not susceptible to suppression. Spleen cells from F1 mice suppressed by parental lymphocyte inoculation were defective in their ability to make I1-2 in culture, and spleen cells from GVH mice appeared to have lost the I1-2 receptors. The immune systems of F1 mice suppressed by GVH were not reconstituted by whole body irradiation and repopulation with F1 spleen or bone marrow.